Development of the urinary system

Overview

The development of the urinary system involves the transient formation and remodeling of the intermediate mesoderm, being the middle germ layer of the developing embryo. During development, three successive pairs of kidneys appear: the pronephros, the mesonephros, and the metanephros. The pronephros appears and subsequently degenerates, the mesonephros becomes temporarily functional before degenerating, and the permanent metanephros ascends from the pelvis to the lumbar region. Concurrently, the urogenital sinus gives rise to the bladder, its neck, the penile urethra, and the vestibule of the vagina.

Pronephros

By week 4, the intermediate mesoderm condenses and reorganizes into a series of epithelial buds. At the cranial level, these buds form the first pair of kidneys, the pronephros (plural, pronephroi). In humans, the pronephros degenerates as rapidly as it forms, providing a glimpse of evolutionary history similar to what is observed in the pharyngeal apparatus. In vertebrates with free-swimming larvae, such as teleost fishes and certain amphibians, the pronephros is the functional kidney of their early larval life and is crucial for proper systemic osmoregulation. Although its rapid degeneration in humans, the formation of the pronephros lays the foundation for induction of the mesonephros, which in turn lays the foundation for induction of the metanephros. Hence, the pronephros is crucial to the developmental cascade that leads to the formation of the permanent kidneys.

While the pronephros forms and degenerates, a small duct appears lateral to the pronephric region. This small duct is a primary excretory duct known as the mesonephric duct (or Wolffian duct). It differentiates in a cranial-to-caudal sequence to eventually connect and open into the walls of the cloaca. This region of fusion is what eventually forms the posterior wall of the future bladder.

Mesonephros

During the degeneration of the pronephros, the epithelial buds at the thoracic and lumbar levels form the second pair of kidneys, the mesonephros (plural, mesonephroi). The mesonephros degenerates at the thoracic level, but persists at the lumbar level. Simultaneously and also at the lumbar level, 20-30 pairs of mesonephric tubules lengthen from the mesonephric buds. Their lateral ends fuse with the mesonephric duct, while their medial ends differentiate into a cup-shaped sac known as the Bowman’s capsule. In turn, the Bowman’s capsule wraps around a knot of capillaries, known as the glomerulus. Together, this forms a rudimentary renal corpuscle, representing an abbreviated version that mirrors the adult nephron.

With the fusion of the lateral tips of mesonephric tubules to the mesonephric duct, a passage from the excretory units to the cloaca opens. The mesonephros thus functions as a temporary excretory system, producing small amounts of urine during week 6-10. After week 10, the mesonephric system ceases to function and completely regresses in females.

Whereas in males, the mesonephric ducts and ductules persist to eventually form important elements of the male genital system, such as the epididymis, the ductus deferens, the seminal vesicles, and the ejaculatory duct.

Metanephros

While the mesonephros functions a temporary excretory system, the definitive kidneys, the metanephros (plural, metanephroi) forms at the sacral level. The formation of the metanephros consists of two structures that are initially separated: the metanephric blastema and the ureteric bud. The metanephric blastema forms on each side of the body axis at the sacral level as a result of a mesenchymal condensation induced by the intermediate mesoderm.

Simultaneously, a ureteric bud evaginates from the caudal end of each mesonephric duct, lengthens, and penetrates its corresponding metanephric blastema. By week 5, the ureteric bud undergoes a sequence of bifurcations and branching to eventually form the renal pelvis, the major and minor calices, and the collecting ducts. On the other hand, the metanephric blastema is what forms the Bowman’s capsule, the proximal convoluted tubules, the loops of Henle, and the distal convoluted tubules. In other words, the ureteric bud and the metanephric blastema respectively form the excretory portions and collecting portions of the permanent kidneys, a process that takes place over a period of ten weeks.

Relocation of the kidneys

During week 6 to week 9, the metanephric kidneys relocate themselves by following a path on both sides of the dorsal aorta. This relocation process is characterized by three mechanisms that occur concurrently: ascension, medial rotation, and revascularization. First, the kidneys ascend from the sacral to the lumbar region. Second, the hilum of each kidney –  initially facing ventrally – rotates medially to face the dorsal aorta. Third, the ascending and medially rotating kidney is progressively revascularized by a series of arterial sprouts from the dorsal aorta: a permanent renal artery is formed in the lumbar region for each kidney, whereas the original renal arteries in the sacral region and the subsequent ones degenerate.

Recall that the right kidney is usually positioned lower than the left kidney, and that is because it does not ascend as high as the left kidney due to the presence of the liver on the right side. Notably, the process of relocation, the formation of the excretory and collecting portions of the metanephric kidneys, and the temporary functioning of the mesonephric system all occur at the same time. Also, realize that because of the ascension of the kidney, the ureter is now much longer than it once was as a ureteric bud in the sacral region.

Bladder and urethra

Recall that the cloaca is divided by the urorectal septum to form the ventral urogenital sinus and the dorsal anorectal canal. The urogenital sinus itself further develops into three distinctive parts: the bladder, the neck, and the phallic segment. The bladder continues to take the shape that we normally see in adults. The neck contributes to the development of the membranous urethra and the prostatic urethra in males and the membranous urethra in females. The phallic segment contributes to the development of the penile urethra in males and the vestibule of the vagina in females. Concurrent with the partitioning of the cloaca, the allantois regresses and forms a ligamentous band known as the urachus or the median umbilical ligament, which runs through the subperitoneal fat from the apex of the bladder to the umbilicus.

Recall also that the caudal ends of the mesonephric ducts are attached to cloaca. While the septation of the cloaca occurs, these caudal ends expand, flatten, and become incorporated into the posterior wall of the presumptive bladder. Once blended in, these caudal ends fuse and migrate caudally until they open into the pelvic urethra, right below the neck of the bladder. Concurrently, the ureters that were once tiny ureteric buds, dissociate themselves from the caudal ends of the mesonephric ducts, migrate cranio-laterally and also become incorporated into the posterior wall. As a result, lying between the openings of the ureters (laterally and superiorly) and the opening of the pelvic urethra (inferiorly) forms a triangular area known as the trigone.